safety and efficacy of aon-d21 in severe community-acquired pneumonia.

Conditions: Community-acquired Pneumonia

Summary: the goal of this clinical trial is to compare the safety and efficacy of aon-d21 versus placebo, both on top of standard of care, in patients with severe community acquired pneumonia admitted to icu (or similar unit). the main questions to answer are: * the safety and tolerability of aon-d21 vs placebo. * the efficacy of aon-d21vs placebo. * the pharmacokinetics of aon-d21. * the pharmacodynamics of aon d21. * to identify biomarkers for patient stratification and analyses in future trials.

this clinical trial will enroll 100 participants, randomized 2:1 (aon-d21:placebo). participants diagnosed with severe community-acquired pneumonia of bacterial or viral origin requiring admission to an intensive care unit or similar setting, will receive either aon-d21 or placebo intravenous infusions for up to 10 days. in addition, participants will receive standard of care as per local guidelines.

Eligibility criteria:
inclusion criteria: * community-acquired pneumonia, confirmed or suspected of bacterial or viral origin. * admitted to an icu (or similar unit). * requiring respiratory support by hfo ≥ 30 l/min with fio2 ≥ 30% or niv or imv or ecmo. * crp ≥ 50 mg/l. * pao2/fio2 ratio ≤ 150 mmhg. * treatment initiation no more than 48 h after initiation of respiratory support (hfo ≥ 30 l/min with fio2 ≥ 30%, niv, imv or ecmo). * written informed consent. * age ≥ 18 years to ≤ 85 years. * body mass index ≥ 17.5 kg/m² and ≤ 40 kg/m². * for female participants of childbearing potential, agreement to use dual methods of contraception until day 60. * for male participants with female partners of childbearing potential, agreement to use barrier method of contraception until day 60 and to refrain from donating sperm during the study and for 3 months after the last infusion. exclusion criteria: * refractory septic shock. * not expected to survive 72 hours. * hospital-acquired or ventilator-associated pneumonia or known or suspected pneumonia due to aspiration or other physical injury or trauma or tuberculosis. * known or suspected hypersensitivity to aon-d21 or any components of the formulation used (e.g., peg, mannitol or edta) or a history of clinically relevant allergy requiring continuous treatment, or of anaphylaxis. * known fibrotic lung disease, bronchiectasis or any other known severe chronic respiratory disease. * active malignant disease. * factors other than a pathogen suspected or confirmed to be causative for the respiratory insufficiency. * hepatocellular injury defined by an alt or ast value ≥ 3 times the uln. known acute or chronic liver disease with child-pugh c (see appendix 13.6.2). * any medical disease or condition that, in the opinion of the investigator(s), compromises the participant's safety or compromises the interpretation of the results. * receiving chronic immunosuppressive therapy in relevant doses. * known immunodeficiency disease/condition. * nursing and pregnant women (defined as the state after conception until the termination of gestation, screened in all women of child-bearing potential with a chorionic gonadotrophin (hcg) blood test (local laboratory). * current or recent participation in an investigational trial. * systemic treatment with any complement inhibitor. * known complement deficiency. * unlikely to remain at the investigational site beyond 96 h.

Keywords: pneumonia community-acquired severe bacterial viral